Accuracy of thymine-thymine dimer bypass by Saccharomyces cerevisiae DNA polymerase η

The Saccharomyces cerevisiae RAD30 gene functions in error-free replication of UV-damaged DNA. RAD30 encodes a DNA polymerase, Pol η, which inserts two adenines opposite the two thymines of a cis-syn thymine-thymine (T-T) dimer. Here we use steady-state kinetics to determine the accuracy of DNA synthesis opposite the T-T dimer. Surprisingly, the accuracy of DNA synthesis opposite the damaged DNA is nearly indistinguishable from that opposite non-damaged DNA, with frequencies of misincorporation of about 10^{- 2} to 10^-3. These studies support the hypothesis that unlike most DNA polymerases, Pol η is able to tolerate distortions in DNA resulting from damage, which then enables the polymerase to utilize the intrinsic base pairing ability of the T-T dimer.